a) Aims: This study proposes to explore the mechanisms responsible for man's ventilatory acclimatization to chronic hypoxemia. b) Background: The hyperventilation obtained upon sojourn to high altitude is currently attributed to hypoxic-induced stimuli from peripheral chemoreceptors, in combination with a near-perfectly compensated, non-inhibitory, normal level of cerebral spinal fluid pH. This current model has also been widely applied to explain ventilatory adaptation in other chronic stages of derangement. Findings recently obtained in our laboratory are inconsistent with current emphasis on the importance of CSF (H ions) regulation as THE regulatory mechanism in chronic hypoxia. c) Design: The study proposes a testing in healthy man of currently accepted hypotheses through a detailed investigation of the total time course of ventilatory acid-base adaptation to moderate hypoxemia in combination with a similar investigation of acid-base regulation during moderate respiratory alkalosis in a normoxic state. Emphasis is directed toward a quantitative assessment of pH regulation and its controlling mechanisms in plasma, LSF and urine. d) Significance: The combination of chronic arterial hypoxemia and respiratory alkalosis is representative of a combination of complex mechanisms operating both in clinical medicine and in healthy man upon sojourn to high altitude. Current hypotheses concerning the mechanisms responsible for sustained ventilatory changes in chronic states have gained wide acceptance and application, although they are based on a variety of speculations. The present study proposes a rigorous testing of these hypotheses.